[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Neoplasia](https://durgical.com/en/general-pathology/#a-neoplasia) › Invasion and metastasis: the metastatic cascade, step by step [General pathology](https://durgical.com/en/general-pathology/) · [Neoplasia](https://durgical.com/en/general-pathology/#a-neoplasia) # Invasion and metastasis: the metastatic cascade, step by step - Process To spread, a cancer cell must let go of its neighbours, break through tissue, travel in vessels and grow in a new organ. Few cells manage all of it. Updated 2026-11-01 ## Key points - Step 1: loss of E-cadherin loosens cell-cell adhesion. - Step 2: matrix metalloproteinases (for example type IV collagenase) degrade the basement membrane and matrix. - Step 3: altered integrins and laminin receptors let cells attach to and crawl through the matrix. - Intravasation, survival in the bloodstream (often coated by platelets), extravasation and colonisation follow. - Seed and soil: the target organ's environment and chemokine receptors decide where metastases grow. - Epithelial-mesenchymal transition (EMT) gives carcinoma cells a motile, mesenchymal behaviour. ## What it is Metastasis is the spread of tumour cells to sites discontinuous with the primary, and it causes most cancer deaths. It is a multistep cascade: detachment, invasion of the extracellular matrix, entry into vessels, survival in the circulation, exit at a distant site and growth there. The process is inefficient: most circulating tumour cells die, which is why the few successful clones have special traits. ## Function - Proteolysis also releases growth factors stored in the matrix, which further feeds the tumour. - Tumour-associated macrophages and fibroblasts help invasion by producing proteases and growth factors. - Chemokine receptors on tumour cells, matched to chemokines in certain organs, partly explain organ preference. ## Step by step - Carcinoma cells lose E-cadherin and detach from their neighbours. - They secrete proteases (matrix metalloproteinases, cathepsins) that break down the basement membrane. - New adhesion molecules (integrins, laminin receptors) let them grip and move through the matrix. - They migrate, guided by motility factors and by fragments of the broken matrix. - They enter lymphatics or small vessels (intravasation). - In the blood many die; survivors clump with platelets and evade immune attack. - They adhere to the endothelium of a distant organ and exit the vessel (extravasation). - In the new site they may stay dormant for years or grow into a metastasis once they recruit vessels. ## Clinical notes - Most patients with cancer die of metastases, not of the primary tumour. - Microscopic metastases may already exist at diagnosis, the rationale for adjuvant therapy after surgery. - A carcinoma of unknown primary is metastatic disease whose primary site stays hidden. - Late recurrence (for example breast cancer years after surgery) reflects dormant disseminated cells. ## Memory aid Let go, dig, swim, survive, climb out, settle: the six verbs of a metastatic cell. ## Test yourself Think of the answer, then tap the question to see it. ## Which adhesion molecule is lost early in carcinoma invasion? E-cadherin, which normally holds epithelial cells together. ## Which enzymes allow tumour cells to cross the basement membrane? Matrix metalloproteinases, such as type IV collagenases, and other proteases like cathepsins. ## What does the seed and soil idea explain? That metastases grow where the organ's environment (receptors, chemokines, growth factors) suits the tumour cell, not just where blood flow takes it. ## Why is metastasis called inefficient? Millions of cells may enter the blood, but most die from shear forces, loss of anchorage or immune attack; only rare clones form metastases. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/invasion-and-metastasis-the-metastatic-cascade-step-by-step/) ## Related - [Pathways of spread and the usual metastatic sites](https://durgical.com/en/general-pathology/pathways-of-spread-and-the-usual-metastatic-sites/) - [Tumour angiogenesis](https://durgical.com/en/general-pathology/tumour-angiogenesis/) - [The hallmarks of cancer](https://durgical.com/en/general-pathology/the-hallmarks-of-cancer/) - [Benign vs malignant tumours: the comparison table](https://durgical.com/en/general-pathology/benign-vs-malignant-tumours-the-comparison-table/) - [How tumours evade the immune system](https://durgical.com/en/general-pathology/how-tumours-evade-the-immune-system/) - [Grading and staging: what TNM means](https://durgical.com/en/general-pathology/grading-and-staging-what-tnm-means/) ## Related conditions - [Breast cancer](https://durgical.com/en/conditions/breast-cancer/) - [Lung cancer](https://durgical.com/en/conditions/lung-cancer/) - [Carcinoma of unknown primary](https://durgical.com/en/conditions/carcinoma-of-unknown-primary/) - [Melanoma](https://durgical.com/en/conditions/melanoma/) - [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/) - [Gastric cancer](https://durgical.com/en/conditions/gastric-cancer/) - [Prostate cancer](https://durgical.com/en/conditions/prostate-cancer/) - [Osteosarcoma](https://durgical.com/en/conditions/osteosarcoma/) ## Elsewhere in DurgiPedia - [Extracellular matrix: collagen types, elastin, ground substance](https://durgical.com/en/histology/extracellular-matrix-collagen-types-elastin-ground-substance/) - [Basement membrane](https://durgical.com/en/histology/basement-membrane/) - [Cell junctions: tight, adherens, desmosomes, gap, hemidesmosomes](https://durgical.com/en/histology/cell-junctions-tight-adherens-desmosomes-gap-hemidesmosomes/) - [How the lymphatic system works](https://durgical.com/en/physiology/how-the-lymphatic-system-works/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [Metastatic Cancer: When Cancer Spreads](https://www.cancer.gov/types/metastatic-cancer) (National Cancer Institute (NCI), 2026); [What Is Cancer?](https://www.cancer.gov/about-cancer/understanding/what-is-cancer) (National Cancer Institute (NCI), 2026); [Angiogenesis Inhibitors](https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet) (National Cancer Institute (NCI), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/invasion-and-metastasis-the-metastatic-cascade-step-by-step/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/invasion-and-metastasis-the-metastatic-cascade-step-by-step/